Protein targeting lysosomal proteins

Lysosomal proteins are also sorted and targeted in the trans-Golgi network 150... 

Von Figura, K. Molecular recognition and targeting of lysosomal proteins. 3 642-646,1991. 

Pfeffer, S.R., Targeting of proteins to the lysosome. Curr Top Microbiol Immunol, 1991.170 43-65. 

Posttranslational modification Examples of posttranslational modification POSTTRANSLATIONAL MODIFICATION OF POLYPEPTIDE CHAINS (p. 440) Many polypeptide chains are covalently modified after translation. Such modifications include trimming excess amino acids, phosphorylation which may activate or inactivate the protein, glycosylation which targets a protein to become part of a plasma membrane or lysosome or be secreted from the cell, or hydroxylation such as that seen in collagen. 

The process whereby newly synthesized proteins are directed to specific locations is referred to as protein targeting. Soluble lysosomal hydrolases are targeted to lysosomes... 

Lysosomal proteins are targeted to the lysosomes via the addition of a mannose 6-phosphate signal that is added in the ds-compartment of the Golgi and is recognized by a receptor protein in the frans-compartment of the Golgi. The protein is then transported by specialized vesicles to a late endosome that later matures into a lysosome. The mannose 6-phosphate receptor recycles back to the Golgi for re-use. 

Cells must ensure that each newly synthesized protein is sorted to its correct location where it can carry out the appropriate function. This process is called protein targeting. In a eukaryotic cell, the protein may be destined to stay in the cytosol, for example an enzyme involved in glycolysis (see Topic J3). Alternatively it may need to be targeted to an organelle (such as a mitochondrion, lysosome, peroxisome, chloroplast or the nucleus) or be inserted into the plasma membrane or exported out of the cell. In bacteria such as E. coli, the protein may stay in the cytosol, be inserted into the plasma membrane or the outer membrane, be sent to the space between these two membranes (the periplasmic space) or be exported from the cell. In both prokaryotes and eukaryotes, if a protein is destined for the cytosol, it is made on free ribosomes in the cytosol and released directly into the cytosol. If it is destined for other final locations, specific protein-targeting mechanisms are involved. 

Not all lysosomal proteins take the normal route of protein targeting some end up being exported by the cell and must be retrieved. This scavenger pathway works as follows. The lysosomal glycoprotein binds to mannose 6-phosphate receptors in the plasma membrane and is internalized again by endocytosis (Fig. 5). This process, called receptor-mediated endocytosis, creates an endocytic vesicle (or endosome) that then delivers the lysosomal protein to the lysosome by fusion (see Topic E4). 

Figure 11.24. Golgi Complex as Sorting Center. The Golgi complex is the sorting center in the targeting of proteins to lysosomes, secretory vesicles, and the plasma membrane. The cis face of the Golgi complex receives vesicles from the ER, and the trans face sends a different set of vesicles to target sites. Vesicles also transfer proteins from one compartment of the Golgi complex to another. [Courtesy of Dr. Marilyn Farquhar.]...

Phosphorylation and sulfation of N-linked oligosaccharides In mammalian cells, mannose-6-phosphate (Man-6-P) residues are used for targeting lysosomal enzymes [27,28]. Many of the N-linked oligosaccharides on lysosomal enzymes and secreted glycoproteins in Dictyostelium contain Man-6-P residues [11,17,29-33]. These proteins are recognized by the cation-independent Man-6-P receptor (which... 

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